[Exogenously induced retinopathies]. / Exogen bedingte Retinopathien.

Exogenously induced retinopathies can be caused by consumation of stimulating substances, systemic or ocular medications, vaccinations, light or irradiation. Some of the effects are transient, whereas other effects induce irreversible toxic reactions. Retinal damage may develop either acutely with obvious relation to the damaging cause, but often may take a long duration of repeated use of a substance or medication. External stimulants (e.g. nicotine, alcohol, poppers, methanol) are the most frequent cause of exogenously induced retinal damage. Side effects from systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK-, ERK-, FLT3-, checkpoint inhibitors, didanosin, pentosanpolysulfat sodium) or intravitreally applied drugs (e.g. antibiotics, VEGF-inhibitors) are less frequent. Ocular side effects associated with vaccinations are rare. Ambient light sources induce no damaging effects on the retina. Incorrect use of technical or medical light sources (e.g. laser pointers) without adherence to safety recommendations or unshielded observation of the sun might induce permanent retinal damage. Local or external irradiation might induce retinal vascular damage resulting in radiation retinopathy.

[Near-infrared Fundus Autofluorescence: Clinical Application and Diagnostic Relevance]. / Nahinfrarot-Autofluoreszenz: klinische Anwendung und diagnostische Relevanz.

Near-infrared autofluorescence (NIA) is a non-invasive retinal imaging technique for examination of the retinal pigment epithelium (RPE) based on the autofluorescence of melanin. Melanin has several functions within the RPE cells, in one of them it serves as a protective antioxidative factor within the RPE cells and is involved in the phagocytosis of photoreceptor outer segments. Disorders that affect the photoreceptor-RPE complex result in alterations of RPE cells which are detectable by alterations of NIA. Therefore, NIA allows to detect early alterations in inherited and acquired chorioretinal disorders, frequently prior to ophthalmoscopical visualisation and often prior to alterations in lipofuscin associated fundus autofluorescence (FAF) or optical coherence tomography (OCT). Although NIA and FAF relate to disorders affecting the RPE, findings between both imaging methods differ and the area involved has been demonstrated to be larger in NIA compared to FAF in several disorders (e.g., age-related macular degeneration, retinitis pigmentosa, ABCA4-gene associated Stargardt disease and cone-rod dystrophy, light damage), indicating that NIA detects earlier alterations compared to FAF. In addition, due to the absence of blue-light filtering which limits foveal visualisation in FAF, foveal alterations can be much better detected using NIA. A reduced subfoveal NIA intensity is the earliest sign of autosomal dominant BEST1-associated disease, when FAF and OCT are still normal. In other disorders, a normal subfoveal NIA intensity is associated with good visual acuity. This review summarizes the present knowledge on NIA and demonstrates biomarkers for various chorioretinal disorders.

[Toxic retinopathies]. / Toxische Retinopathien.

Toxic retinopathies are most frequently induced by external stimulants (e.g. nicotine, poppers, methanol) and are less frequently undesired side effects of systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK, ERK, FLT3 or checkpoint inhibitors, didanosine, pentosan polysulfate sodium) or intravitreally applied drugs. The clinical symptoms of undesired side effects of drugs are often similar to retinal diseases from other causes, which interferes with the recognition of the undesired side effects of drugs. Clinical findings, pathophysiological mechanisms and if advisable strategies for screening are discussed. The focus is on the presentation of confirmed undesirable side effects with established associations for medications which have long been approved. For novel medications, in addition potential but not proven associations are presented to facilitate the recognition of additional cases with side effects for these medications.

[Congenital Retinal Dystrophies: Combining Ophthalmological Techniques to Improve the Read-out]. / Hereditäre Netzhautdystrophien: Kombination ophthalmologischer Methoden zur Optimierung des Readout.

An early diagnosis, differential diagnosis and possible decision about therapeutic interventions has considerable consequences for the personal and social life of patients affected with inherited retinal dystrophies (IRD). For the ophthalmologist, the clinical heterogeneity interferes with a simple diagnostic approach. The present review suggests a structured clinical approach for the ophthalmological diagnosis of IRD and discusses the relevance of different methods for diagnosis, differential diagnosis and the evaluation of progression. A detailed history should be followed by non-invasive retinal imaging. An early diagnosis prior to visible fundus alterations is facilitated by combining optical coherence tomography, fundus and near-infrared autofluorescence. Spectral reflectance photography, OCT angiography and fluorescence lifetime imaging ophthalmoscopy are helpful in the early diagnosis of specific IRD. If retinal imaging is not sufficient for a diagnosis the multifocal electroretinogram is useful for early diagnosis and full-field electroretinogram for differential diagnosis of IRD. Patients should be referred to specialised IRD-centres for differential diagnosis and possible treatment.

Fundus Autofluorescence and SD-OCT Document Rapid Progression in Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC) Associated with a c.256G > A Mutation in BEST1.

PURPOSE: To report the variability of clinical findings, rapid concentric progression, and successful treatment of macular edema in autosomal dominant vitreoretinochoroidopathy (ADVIRC) associated with a heterozygous c.256G > A missense mutation in the bestrophin-1 (BEST1) gene. METHODS: Three affected members of a four-generation ADVIRC family were examined with fundus autofluorescence (FAF), near-infrared autofluorescence (NIA) and spectral domain optical coherence tomography (SD-OCT). Direct sequence analysis of coding and flanking intronic regions of the BEST1 gene was performed. RESULTS: Disease manifestations presented with high variability with visual problems manifesting between 10 and 40 years of age. Two probands showed marked signs of peripheral degeneration, while this retinal area was not noticeably affected in the third. Cystoid macular edema was present in one proband, which responded to long-term treatment with topic dorzolamide with improved visual acuity. FAF and NIA revealed mid-peripheral retinal degeneration in areas that appeared normal on ophthalmoscopy. The full-field ERG was markedly reduced in two probands. Within a 5-year period a marked increase in concentric progression of degeneration including the posterior pole was documented with FAF, NIA and SD-OCT in one proband after the age of 63 years. Direct sequence analysis of the BEST1 gene revealed a heterozygous c.256G > A missense mutation in the three affected probands. CONCLUSION: The findings in this family emphasize the previously noted variability of clinical manifestations in BEST1-associated ADVIRC and the relevance of FAF and NIA imaging. Cystoid macular edema and vascular leakage can be successfully treated using dorzolamide.

Cystoid macular oedema and epiretinal membrane formation during progression of chloroquine retinopathy after drug cessation.

AIMS: To evaluate progression of morphological alterations in chloroquine (CQ) or hydroxychloroquine (HCQ) retinopathy after drug cessation. METHODS: Eleven female patients (age range at drug cessation 46-78 years; treatment duration 5-20 years) were examined between 2.1 and 7.1 years after drug cessation. In addition to clinical examination, they underwent high-resolution optical coherence tomography (OCT) (spectral domain OCT (SD-OCT); Spectralis OCT, Heidelberg Engineering, Germany), fundus autofluorescence (FAF), near-infrared autofluorescence (NIA; HRA2, Heidelberg Engineering, Germany) and ultra-wide-angle fundus autofluorescence (UW-FAF; Optos 200Tx; Optos PLC, UK). RESULTS: Two patients with very limited parafoveal retinopathy did not present with progression within 3 years. In the remaining nine patients, visual acuity deteriorated and progression of retinal degeneration could be documented. FAF, UW-FAF and NIA changes included an increase of affected area or a regional increase or decrease of FAF or NIA intensity. SD-OCT changes included reduction of retinal thickness, an increased area of photoreceptor or retinal pigment epithelial loss, development or increase of cystoid macular oedema (4/9) or development of epiretinal membranes (5/9). Therapy of cystoid macular oedema was of limited benefit. CONCLUSIONS: CQ retinopathy can progress over a long period of time after drug cessation and may be complicated by cystoid macular oedema, epiretinal membrane formation and peripheral involvement.

Fundus autofluorescence (488 NM) and near-infrared autofluorescence (787 NM) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration.

PURPOSE: The purpose of this study was to compare near-infrared fundus autofluorescence(NIA, excitation 787 nm, emission >800 nm) with fundus autofluorescence (FAF,excitation 488 nm, emission >500 nm) in patients with age-related macular degeneration(AMD). METHODS: Fundus autofluorescence and NIA were obtained using a confocal scanning laser ophthalmoscope (HRA2) in 308 eyes (172 patients) with AMD [age-related maculopathy(n 116), geographic atrophy (n 77), and neovascular AMD (n 115)]. RESULTS: Retinal pigment epithelial alterations were detected with FAF and NIA in all eyes and showed a similar lesion size in 81.8%. In age-related maculopathy, spots of increased FAF (87.9%) were more frequent than spots of reduced FAF (26.7%). Spots of increased and reduced NIA were of similar frequency (66.4%). A higher relative intensity of FAF was more frequent (72.4%) than higher relative NIA intensity (16.4%), suggesting that loss of NIA usually precedes loss of FAF. The junctional zone of geographic atrophy presented with increased NIA (19.5%), increased FAF (10.4%), or an increase of both(22.1%). In neovascular AMD, exudative changes were better visualized with FAF (56.5%)compared with NIA (33.9%). CONCLUSION: Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin in the pathophysiological process and provide further insight into the development of AMD and noninvasive monitoring of future therapeutic interventions.

Lipofuscin- and melanin-related fundus autofluorescence in patients with ABCA4-associated retinal dystrophies.

PURPOSE: To compare melanin-related near-infrared fundus autofluorescence (NIA; excitation 787 nm, emission > 800 nm) to lipofuscin-related fundus autofluorescence (FAF; excitation 488 nm, emission > 500 nm) in patients with retinal dystrophies associated with ABCA4 gene mutations (ABCA4-RD). DESIGN: Observational case series. METHODS: Sixteen consecutive patients with ABCA4-RD diagnosed in one institution were included. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Heidelberg, Germany). The pattern and size of retinal pigment epithelial (RPE) alterations detected with FAF and NIA were evaluated. RESULTS: FAF and NIA alterations were detected in all patients. In 7 of 16 patients, the alterations progressed beyond the vascular arcades, and in 9 of 16, they were confined to the macula. Spots of increased NIA (4/16) were less frequent compared with spots of increased FAF (15/16). Confluent patches of reduced NIA were frequent (12/16), and severely reduced NIA was observed in 3 cases. Areas with reduced NIA corresponded to either increased or reduced FAF. Preservation of subfoveal FAF or NIA corresponded to visual acuity > or = 0.4. Abnormalities detected with NIA were more extensive or more severe compared to FAF in 15 of 16 patients. CONCLUSION: Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin and their derivates in the pathophysiologic process of ABCA4-RD. NIA imaging provides a noninvasive in vivo visualization of RPE abnormalities that may precede FAF alterations during the degenerative process. Combined FAF and NIA imaging will provide further insight in the development of ABCA4-RD and could help to monitor future therapeutic interventions.

Chloroquine retinopathy: lipofuscin- and melanin-related fundus autofluorescence, optical coherence tomography and multifocal electroretinography.

PURPOSE: To evaluate melanin-related near-infrared fundus autofluorescence (NIA, excitation 787 nm, emission > 800 nm), lipofuscin-related fundus autofluorescence (FAF, excitation 488 nm, emission >500 nm), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) in patients with chloroquine (CQ) retinopathy. METHODS: Two patients with progressed CQ retinopathy underwent clinical examination, ISCEV mfERG evaluation, and FAF and NIA imaging using a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2) with either a 30 degrees or wide-angle field-of-view. OCT3 imaging was performed in one of these patients. RESULTS: In the foveola, FAF and NIA were relatively normal. Parafoveal loss of retinal pigment epithelium (RPE) was indicated by absent FAF and NIA. An area of reduced FAF and NIA surrounded the parafoveal region of RPE loss. In the adjacent area, FAF was increased and increased NIA marked the peripheral border of increased FAF. Wide-field imaging revealed increased FAF in association with retinal vessels. Retinal thickness was markedly reduced in the OCT predominantly in the parafoveal region. Visual field loss and mfERG amplitude reduction corresponded to areas with increased or reduced FAF and NIA. CONCLUSION: Patterns of FAF and NIA indicate different stages of pathophysiologic processes involving lipofuscin and melanin in the RPE. Combined retinal imaging and functional testing provides further insights in the pathogenesis and development of retinal degenerative disease. An association of CQ retinopathy with retinal vessels architecture is hypothesized.